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CD8+T cell metabolic flexibility elicited by CD28-ARS2 axisdriven alternative splicing of PKM supports antitumor immunity

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Cellular & Molecular Immunology 2024年第3期21卷 260-274页

作者： G.Aaron holling Colin A.Chavel Anand P.Sharda Mackenzie M.lieberman Caitlin M.James Shivana M.lightman Jason h.Tong Guanxi Qiao Tiffany R.Emmons Thejaswini Giridharan Shengqi hou Andrew M.Intlekofer Richard M.higashi Teresa W.M.Fan Andrew N.lane kevin h.eng.brahm h.seg.l Elizabeth A.Repasky Kelvin P.lee Scott h.Olejniczak Department of Immunology Roswell Park Comprehensive Cancer CenterBuffaloNY 14263USA Department of Medicine Roswell Park Comprehensive Cancer CenterBuffaloNY 14263USA human Oncology and Pathogenesis Program Memorial Sloan Kettering Cancer CenterNew YorkNY 10065USA Center for Environmental Systems Biochemistry Department of Toxicology and Cancer Biology and Markey Cancer CenterLexingtonKY 40536USA Department of Cancer Genetics and Genomics Roswell Park Comprehensive Cancer CenterBuffaloNY 14263USA Present address:University of Colorado Boulder BoulderCO 80309USA Present address:Dana Farber Cancer Institute BostonMA 02215USA Present address:Massachusetts Institute of Technology BostonMA 02139USA Present address:Melvin and Bren Simon Comprehensive Cancer Center Indiana University School of MedicineIndianapolisIN 46202USA

Metabolic flexibility has emerged as a critical determinant of CD8+T-cell antitumor activity,yet the mechanisms driving the metabolic flexibility of T cells have not been *** this study,we investigated the influence of the nuclear cap-binding complex(CBC)adaptor protein ARS2 on mature T *** doing so,we discovered a novel signaling axis that endows activated CD8+T cells with flexibility of glucose ***2 upregulation driven by CD28 signaling reinforced splicing factor recruitment to pre-mRNAs and affected approximately one-third of T-cell activation-induced alternative splicing *** these effects,the CD28-ARS2 axis suppressed the expression of the M1 isoform of pyruvate kinase in favor of PKM2,a key determinant of CD8+T-cell glucose utilization,interferon gamma production,and antitumor effector ***,PKM alternative splicing occurred independently of CD28-driven PI3K pathway activation,revealing a novel means by which costimulation reprograms glucose metabolism in CD8+T cells.

关键词： Immunometabolism mRNA splicing CD8 T cells ARS2 PKM2

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Disparate outcomes in hispanic patients with metabolic dysfunctionassociated steatotic liver disease/steatohepatitis and type 2 diabetes: large cohort study

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World Journal of Diabetes 2024年第5期15卷 886-897页

作者： Joseph Matthew Gosnell George Golovko Esteban Arroyave Akshata Moghe Michael l Kueht Omar AbdulSaldarriaga kevin h McKinney heather l Stevenson Monique R Ferguson Department of Pathology University of Texas Medical BranchGalvestonTX 77555United States Department of Pharmacology&Toxicology University of Texas Medical BranchGalvestonTX 77555United States Department of Medicine University of Texas Health Science Center at HoustonHoustonTX 77030United States Department of Surgery University of Texas Medical BranchGalvestonTX 77555United States Center for Tropical Diseases Department of Internal MedicineUniversity of Texas Medical BranchGalvestonTX 77555United States Department of Internal Medicine University of Texas Medical BranchGalvestonTX 77555United States

BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASlD)and metabolic dysfunction-associated steatohepatitis(MASh)are a growing health burden across a significant portion of the global patient ***,these conditions seem to have disparate rates and outcomes between different ethnic *** combination of MASlD/MASh and type 2 diabetes increases the risk of hepatocellular carcinoma(hCC),and hispanic patients experience the greatest burden,particularly those in South *** To compare outcomes between hispanic and non-hispanic patients in the United States,while further focusing on the hispanic population within Southeast Texas to determine whether the documented disparity in outcomes is a function of geographical circumstance or if there is a more widespread reason that all clinicians must account for in prognostic *** This cohort analysis was conducted with data obtained from TriNetX,llC(“TriNetX”),a global federated health research network that provides access to deidentified medical records from healthcare organizations *** cohort networks were used:University of Texas Medical Branch(UTMB)hospital and the United States national database collective to determine whether disparities were related to geographic regions,like Southeast *** This study findings revealed hispanics/latinos have a statistically significant higher occurrence of hCC,type 2 diabetes mellitus,and liver fibrosis/cirrhosis in both the United States and the UTMB hispanic/latino *** mortality in hispanics/latinos was lower within the United States group and not statistically elevated in the UTMB *** This would appear to support that hispanic patients in Southeast Texas are not uniquely affected compared to the national hispanic population.

关键词： Metabolic dysfunction-associated steatotic liver disease Metabolic dysfunction-associated steatohepatitis hispanic Diabetes mellitus TriNetX Non-alcoholic fatty liver disease Non-alcoholic steatohepatitis Steatotic liver disease hepatocellular carcinoma

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A thermodynamic perspective on electrode poisoning in solid oxide fuel cells

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International Journal of Minerals,Metallurgy and Materials 2024年第6期31卷 1449-1455页

作者： kevin huang Department of Mechanical engineering University of South CarolinaColumbiaUSA

A critical challenge to the commercialization of clean and high-efficiency solid oxide fuel cell(SOFC)technology is the insuf-ficient stack lifespan caused by a variety of degradation mechanisms,which are associated with cell components and chemical *** components related degradation refers to thermal/chemical/electrochemical deterioration of cell materials under operating conditions,whereas the latter regards impurities in feedstocks of oxidant(air)and reductant(fuel).This article provides a thermodynamic perspective on the understanding of the impurities-induced degradation mechanisms in *** discussion focuses on using thermodynamic ana-lysis to elucidate poisoning mechanisms in cathodes by impurity species such as Cr,CO_(2),h_(2)O,and SO_(2) and in the anode by species such as S(or h_(2)S),SiO_(2),and P_(2)(or Ph_(3)).The author hopes the presented fundamental insights can provide a theoretical foundation for search-ing for better technical solutions to address the critical degradation challenges.

关键词： impurities air fuel reaction activity

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Numerical Study of Semidiscrete Penalty Approach for Stabilizing Boussinesq System with localized Feedback Control

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Annals of Applied Mathematics 2024年第2期40卷 191-218页

作者： Mejdi Azaiez kevin le Balc'h Universite de Bordeaux Bordeaux-INPI2M UMR5295F-33400TalenceFrance Inria Sorbonne UniversiteUniversite de ParisCNRSLaboratoire Jacques-Louis LionsParisFrance

We investigate the numerical approximation for stabilizing the semidiscrete linearized Boussinesq system around an unstable stationary *** is attained through internal feedback controls applied to the velocity and temperature equations,localized within an arbitrary open *** study follows the framework presented in[14],considering the continuous linearized Boussinesq *** primary objective is to explore the penalizationbased approximation of the free divergence condition in the semidiscrete case and provide a numerical validation of these results in a two-dimensional setting.

关键词： Boussinesq system penalty method stabilization feedback control

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Canonical and noncanonical Wnt signaling: Multilayered mediators, signaling mechanisms and major signaling crosstalk

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Genes & Diseases 2024年第1期11卷 103-134页

作者： kevin Qin Michael Yu Jiaming Fan hongwei Wang Piao Zhao Guozhi Zhaoo Wei Zeng Connie Chen Yonghui Wang Annie Wang Zander Schwartz Jeffrey hong lily Song William Wagstaff Rex C.haydon hue h.luu Sherwin h.ho Jason Strelzow Russell R.Reid Tong-Chuan he lewis l.Shi Chicago Medical School Rosalind Franklin University of Medicine and ScienceNorth ChicagoIL 60064USA Molecular Oncology laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Ministry of Education Key laboratory of Diagnostic Medicine and Department of Clinical BiochemistryThe School of Laboratory MedicineChongqing Medical UniversityChongqing 400016China Departments of Orthopaedic Surgery and Urology The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Interventional Neurology The First Dongguan Affiliated HospitalGuangdong Medical UniversityDongguanGuangdong 523475China Department of Clinical laboratory Medicine Shanghai Jiaotong University School of MedicineShanghai 200000China School of Biomedical engineering Vanderbilt UniversityNashvilleTN 37235USA laboratory of Craniofacial Biology and Development Department of Surgery Section of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA

Wnt signaling plays a major role in regulating cell proliferation and *** Wnt ligands are a family of 19 secreted glycoproteins that mediate their signaling effects via binding to Frizzled receptors and lRP5/6 coreceptors and transducing the signal either throughβ-catenin in the canonical pathway or through a series of other proteins in the nonca-nonical *** of the individual components of both canonical and noncanonical Wnt signaling have additional functions throughout the body,establishing the complex interplay between Wnt signaling and other signaling *** crosstalk between Wnt signaling and other pathways gives Wnt signaling a vital role in many cellular and organ ***-regulation of this system has been implicated in many diseases affecting a wide array of organ systems,including cancer and embryological defects,and can even cause embryonic *** complexity of this system and its interacting proteins have made Wnt signaling a target for many therapeutic ***,both stimulatory and inhibitory treatments come with potential risks that need to be *** review synthesized much of the current knowl-edge on the Wnt signaling pathway,beginning with the history of Wnt *** thoroughly described the different variants of Wnt signaling,including canonical,noncanonical Wnt/PCP,and the noncanonical Wnt/Ca2+*** description involved each of its components and their involvement in other cellular ***,this review explained the various other pathways and processes that crosstalk with Wnt signaling.

关键词： β-catenin Canonical Wnt Noncanonical Wnt Signal transduction Signaling crosstalk

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The evolving roles of Wnt signaling in stem cell proliferation and differentiation, the development of human diseases, and therapeutic opportunities

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Genes & Diseases 2024年第3期11卷 155-187页

作者： Michael Yu kevin Qin Jiaming Fan Guozhi Zhao Piao Zhao Wei Zeng Connie Chen Annie Wang Yonghui Wang jiamin Zhong Yi Zhu William Wagstaff Rex C.haydon hue h.luu Sherwin ho Michael J.lee Jason Strelzow Russell R.Reid Tong-Chuan he School of Medicine Rosalind Franklin University of Medicine and ScienceNorth ChicagoIL 60064USA Molecular Oncology laboratory Department of Orthopedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Ministry of Education Key laboratory of Diagnostic Medicine and Department of Clinical BiochemistryThe School of Laboratory MedicineChongqing Medical UniversityChongqing 400016China Department of Orthopedic Surgery The First Affliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Urology The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Clinical laboratory Medicine Shanghai Jiaotong University School of MedicineShanghai 200000China Department of Orthopaedic Surgery Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China laboratory of Craniofacial Suture Biology and Development Department of Surgery Section of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA Department of Neurology The First Dongguan Affiliated HospitalGuangdong Medical UniversityDongguanGuangdong 523475China

The evolutionarily conserved Wnt signaling pathway plays a central role in develop-ment and adult tissue homeostasis across *** proteins are secreted,lipid-modified signaling molecules that activate the canonical(β-catenin dependent)and non-canonical(β-catenin independent)Wnt signaling *** behaviors such as proliferation,differ-entiation,maturation,and proper body-axis specification are carried out by the canonical pathway,which is the best characterized of the known Wnt signaling *** signaling has emerged as an important factor in stem cell biology and is known to affect the self-renewal of stem cells in various *** includes but is not limited to embryonic,hematopoietic,mesenchymal,gut,neural,and epidermal stem *** signaling has also been implicated in tumor cells that exhibit stem cell-like *** signaling is crucial for bone formation and presents a potential target for the development of therapeutics for bone *** surprisingly,aberrant Wnt signaling is also associated with a wide variety of diseases,including *** of Wnt pathway members in cancer can lead to unchecked cell proliferation,epithelial-mesenchymal transition,and ***,advances in the understand-ing of dysregulated Wnt signaling in disease have paved the way for the development of novel therapeutics that target components of the Wnt *** with a brief overview of the mechanisms of canonical and non-canonical Wnt,this review aims to summarize the cur-rent knowledge of Wnt signaling in stem cells,aberrations to the Wnt pathway associated with diseases,and novel therapeutics targeting the Wnt pathway in preclinical and clinical studies.

关键词： β-Catenin Cancer Canonical Wnt Disease Non-canonical Wnt Stem cells Targeted therapy Wnt signaling

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Potential transformation of organic matter by microbes in cryoconite,Tibetan Plateau

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Science China Earth Sciences 2024年第6期67卷 1978-1989页

作者： Bixi GUO Yongqin lIU kevin Xu ZhONG Quan ShI Chen hE Qiang Zheng Ruanhong CAI State Key laboratory of Tibetan Plateau Earth System Environment and Resources(TPESER)Institute of Tibetan Plateau ResearchChinese Academy of SciencesBeijing 100101China Center for the Pan-Third Pole Environment Lanzhou UniversityLanzhou 730000China Department of Earth Oceanand Atmospheric SciencesUniversity of British ColumbiaVancouverBC V6T 1Z4Canada State Key laboratory of heavy Oil Processing Petroleum Molecules Engineering Center(PMEC)China University of PetroleumBeijing 102249China State Key laboratory for Marine Environmental Science Collage of Ocean and Earth SciencesXiamen UniversityXiamen 361102China Fujian Key laboratory of Marine Carbon Sequestration Xiamen UniversityXiamen 361005China

Microorganisms play an essential role in the glacier carbon cycle;how they transform organic matter in mountain glacial cryoconite remains to be ***,we applied ultra-high resolution Fourier transform ion cyclotron resonance mass spectrometry(FT-ICR MS)and deep sequencing of 16S rRNA gene,to investigate the temporal microbial transformation of dissolved organic matter(DOM)of the Tibetan Plateau *** the 60-day incubation,we found that DOM in cryoconite underwent a three-stage transformation,with decreasing bioavailability over *** microbial community did not change much in the first week while degrading DOM molecules that were associated with higher h/C_(wa)and lower O/C_(wa).During days 15-30,DOM composition remained stable while microbial diversity *** day 60,the DOM was microbially converted into a higher state of recalcitrance,with higher values of aromatic index,O/C_(wa),and lower h/C_(wa),which contained molecules containing more *** among various microbial taxa,like Cyanobacteria,Bacteroidota,Gammaproteobacteria,Firmicutes,and Actinobacteriota,drove the DOM transformation in *** study sheds light on the in-situ transformation of DOM composition meditated by microbial populations in cryoconite at a temporal scale,providing new insights into understanding the microbial roles in the glacier organic carbon transformation.

关键词： Cryoconite Dissolved organic matter Biodegradation Microbial community Temporal variation

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Rational Design and Construction of a CdS QDs/InVO4 Atomic-layer（110）/（110） Facet S-Scheme heterojunction for highly Efficient Photocatalytic Degradation of C2h4

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Energy & Environmental Materials 2024年第3期7卷 215-222页

作者： Yuanpeng Dong Peizhu Ji Xinyue Xu Rong li Yin Wang kevin Peter homewood Xiaohong Xia Yun Gao Xuxing Chen Ministry of Education Key laboratory for the Green Preparation and Application of Functional Materials School of Materials Science&Engineering Hubei University hubei Key laboratory of low Dimensional Optoelectronic Materials and Devices Hubei University of Arts and Science State Key laboratory of Structural Chemistry Fujian Institute of Research on the Structure of Matter Chinese Academy of Sciences United Water (Xianning) Company limited

Exploring high efficiency S-scheme heterojunction photocatalysts with strong redox ability for removing volatile organic compounds from the air is of great interest and ***,how to predict and regulate the transport of photogenerated carriers in heterojunctions is a great ***,density functional theory calculations were first used to successfully predict the formation of a CdS quantum dots/InVO4atomic-layer （110）/（110） facet S-scheme ***,a CdS quantum dots/InVO4atomic-layer was synthesized by in-situ loading of CdS quantum dots with （110） facets onto the（110） facets of *** a result of the deliberately constructed built-in electric field between the adjoining facets,we obtain a remarkably enhanced photocatalytic degradation rate for *** rate is 13.8 times that of pure CdS and 13.2 times that of pure ***-situ irradiated X-ray photoelectron spectroscopy,photoluminescence and time-resolved photoluminescence measurements were carried *** experiments validate that the built-in electric field enhanced the dissociation of photoexcited excitons and the separation of free charge carriers,and results in the formation of S-scheme charge transfer *** reaction mechanism of the photocatalytic C2h4oxidation is investigated by in-situ electron paramagnetic *** work provides a mechanistic insight into the construction and optimization of semiconductor heterojunction photocatalysts for application to environmental remediation.

关键词： CdS QDs InVO4 atomic-layer photocatalysis S-scheme volatile organic compounds

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Multinuclear MR and MRI study of lithium-ion cells using a variable field magnet and a fixed frequency RF probe

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Magnetic Resonance letters 2024年第1期4卷 10-20页

作者： Andrés Ramírez Aguilera Florin Marica kevin J.Sanders Md Al Raihan C.Adam Dyker Gillian R.Goward Bruce *** UNB MRI Centre Department of PhysicsUniversity of New BrunswickFrederictonNew BrunswickE3B 5A3Canada Department of Chemistry McMaster UniversityHamiltonOntarioL8S 4L8Canada Department of Chemistry University of New BrunswickFrederictonNew BrunswickE3B 5A3Canada

An exploratory multinuclear magnetic resonance(MR)and magnetic resonance imaging(MRI)study was performed on lithium-ion battery cells with ^(7)li,^(19)F,and ^(1)h measurements.A variable field superconducting magnet with a fixed frequency parallel-plate radiofrequency(RF)probe was employed in the *** magnetic field was changed to set the resonance frequency of each nucleus to the fixed RF probe frequency of 33.7 *** cartridge-like lithium-ion cells,with graphite anodes and liNi_(0.5)Mn_(0.3)Co_(0.2)O_(2)(NMC)cathodes,were *** cell was pristine,and one was charged to a cell voltage of 4.2 *** results presented demonstrate the great potential of the variable field magnet approach in multinuclear measurement of lithium-ion *** methods open the door for developing faster and simpler methods for detecting,quantifying,and interpreting MR and MRI data from lithium-ion and other batteries.

关键词： Multinuclear MR/MRI Variable field magnet lithium-ion battery Parallel-plate rf probe

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Genetic analyses of ancient tea trees provide insights into the breeding history and dissemination of Chinese Assam tea(Camellia sinensis ***)

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Plant Diversity 2024年第2期46卷 229-237页

作者： Miao-Miao li Muditha K.Meegahakumbura Moses C.Wambulwa kevin S.Burgess Michael Möller Zong-Fang Shen De-Zhu li lian-Ming Gao CAS Key laboratory for Plant Diversity and Biogeography of East Asia Kunming Institute of BotanyChinese Academy of ScienceKunming650201China Germplasm Bank of Wild Species Kunming Institute of BotanyChinese Academy of ScienceKunming650201China Kunming College of life Science University of Chinese Academy of SciencesKunming650201YunnanChina Department of Export Agriculture Faculty of Animal Science and Export AgricultureUva Wellassa UniversityBadulla90000Sri Lanka Department of life Sciences School of Science and ComputingSouth Eastern Kenya University170-90200KituiKenya Department of Biology Columbus State UniversityUniversity System of GeorgiaColumbusGA31907-5645USA Royal Botanic Garden Edinburgh 20A Inverleith RowEdinburghEH35LRScotlandUK lijiang Forest Biodiversity National Observation and Research Station Kunming Institute of BotanyChinese Academy of SciencesLijiang674100YunnanChina

Chinese Assam tea(Camellia sinensis ***)is an important tea crop with a long history of cultivation in Yunnan,*** its potential value as a genetic resource,its genetic diversity and domestication/breeding history remain *** address this issue,we genotyped 469 ancient tea plant trees representing 26 *** *** populations,plus two of its wild relatives(six and three populations of *** and ***,respectively)using 16 nuclear microsatellite *** showed that Chinese Assam tea has a relatively high,but comparatively lower gene diversity(h_(S)=0.638)than the wild relative ***(h_S=0.658).Clustering in STRUCTURE indicated that Chinese Assam tea and its two wild relatives formed distinct genetic groups,with considerable interspecific *** Chinese Assam tea accessions clustered into three gene pools,corresponding well with their geographic ***,New hybrids analysis indicated that 68.48%of ancient Chinese Assam tea plants from Xishuangbanna were genetic intermediates between the Puer and lincang gene *** addition,10%of the ancient Chinese Assam tea individuals were found to be hybrids between Chinese Assam tea and *** results suggest that Chinese Assam tea was domesticated separately in three gene pools(Puer,lincang and Xishuangbanna)in the Mekong River valley and that the hybrids were subsequently selected during the domestication *** the domestication history of Chinese Assam tea in southwestern Yunnan remains complex,our results will help to identify valuable genetic resources that may be useful in future tea breeding programs.

关键词： Tea plant hybrid origin Genetic diversity Domestication history Camellia sinensis var.assamica Camellia taliensis

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